PROJECT SUMMARY Plasmodium falciparum causes the deadliest form of malaria, which is responsible for nearly one million deaths annually. There is currently no perfect test to detect if a person has malaria. This is because all available tests have challenges and are all based on testing a blood sample. We have identified volatile organic compounds that are produced by the malaria parasite in culture. In a recent pilot study that was conducted in Lilongwe, Ma- lawi, we found that similar compounds are also present in the breath of children who have uncomplicated falci- parum malaria. We also observed a global change in the breath profile of children with malaria. The objectives of this proposal are to identify candidate biomarkers of malaria, with the long-term goal to develop a new non- invasive test to diagnose clinical malaria infection. Supported by our strong preliminary data that indicate that this strategy will be successful, our objectives will be met through two specific aims: 1) determine reproducible changes in the breath composition in response to malaria infection, in an independent location. 2) Relate breath changes with parasite development stages. Our approach is innovative, since we will enroll naturally infected children in the field. Children harbor the highest parasite and gametocyte densities. The proposed re- search is significant, because we will progress in development of new, much-needed malaria diagnostic tool that will not rely on blood samples.